Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the presence and morphology of plaque-like lesions in the frontal cortex of six patients, aged 40 to 76 years, with hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D), using beta/A4 immuno-, silver, Congo red and thioflavin S staining. Two types of beta/A4 immunoreactive and Congo red-negative plaques were detected. The first type was composed of argyrophilic fibrous material in periodic acid-methenamine silver (PAM) and modified Bielschowsky staining and lacked silver-stained degenerating neurites. Therefore, this type of plaque has the same staining properties as the diffuse plaque described in Alzheimer's disease, Down's syndrome and nondemented elderly. The second type of plaque, occurring only in the three oldest patients and numerically increasing with age, consisted of a spherical non-argyrophilic area of granular texture with a rim of PAM-positive material. The PAM-positive fibrous material of both types of plaques was mingled with coarser and compact, irregular-shaped argyrophilic structures in the oldest patient. The described plaques did not show bright fluorescence with thioflavin S staining. These results indicate, that the morphology of plaques, encountered in HCHWA-D, is diverse and changes with age.
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PMID:Morphology of cerebral plaque-like lesions in hereditary cerebral hemorrhage with amyloidosis (Dutch). 147 74

The amyloid beta-protein is a 39-42 amino acid peptide that is deposited in senile plaques and in cerebral vessel walls in individuals with Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), and, to a much lesser extent, normal aging. It is derived from abnormal proteolytic processing of its parent protein, the amyloid beta-protein precursor. Here we show that individuals with the HCHWA-D mutation and clinically manifesting the disease have markedly decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (0.7 +/- 0.4 micrograms/ml) compared with age-matched normal subjects (3.0 +/- 0.2 micrograms/ml) as determined by quantitative immunoblotting and enzyme-linked immunosorbent assays. Similarly, age-matched patients diagnosed with probable Alzheimer's disease also have decreased cerebrospinal fluid levels of soluble amyloid beta-protein precursor (1.0 +/- 0.3 micrograms/ml). These parallel findings suggest a common biochemical marker for these two diseases and further establish the pathogenic relatedness of HCHWA-D and Alzheimer's disease.
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PMID:Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal fluid levels of amyloid beta-protein precursor. 151 Mar 61

Human hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), an autosomal dominant form of cerebral amyloid angiopathy (CAA), is characterized by extensive amyloid deposition in the small leptomeningeal arteries and cortical arterioles, which lead to an early death of those afflicted in their fifth or sixth decade. Immunohistochemical and biochemical studies have indicated that the amyloid subunit in HCHWA-D is antigenically related to and homologous in sequence with the amyloid beta protein isolated from brains of patients with Alzheimer's disease and Down syndrome. The amyloid beta protein is encoded by the amyloid beta protein precursor (APP) gene located on chromosome 21. Restriction fragment length polymorphisms detected by the APP gene were used to examine whether this gene is a candidate for the genetic defect in HCHWA-D. The data indicate that the APP gene is tightly linked to HCHWA-D and therefore, in contrast to familial Alzheimer's disease, cannot be excluded as the site of mutation in HCHWA-D.
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PMID:Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). 197 58

Amyloid fibrils deposited in cerebral vessel walls in Dutch patients with hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) are formed by polymerization of a 39-residue peptide similar to the beta-protein of Alzheimer's disease, Down syndrome, sporadic cerebral amyloid angiopathy and normal aging. Sequence analysis of genomic DNA in HCHWA-D patients demonstrated a point mutation, cytosine for guanine at position 1852 of the precursor beta-protein gene, which causes a single amino acid substitution (glutamine for glutamic acid) corresponding to position 22 of the amyloid protein. The normal allele was also present in these patients. To examine the expression of normal and variant beta-protein alleles in HCHWA-D we analyzed all the tryptic peptides obtained from several amyloid fractions from leptomeningeal vascular walls. Amino acid sequence of two peptides (T3a and T3b) with identical amino acid composition revealed that T3a had glutamine and T3b had glutamic acid at position 22. Thus both the normal and variant Alzheimer's beta-protein alleles are expressed in vascular amyloid in HCHWA-D and may be detected by tryptic peptide mapping. Moreover, we have developed a diagnostic assay for high risk populations and prenatal evaluation that is based on the existence of the mutation.
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PMID:Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. 219 78

Using immunohistochemical staining methods with antibodies to amyloid beta protein and human cystatin C, we examined cerebrovascular amyloid protein in the brains from 46 cases with cerebral amyloid angiopathy (seven with Alzheimer's disease, one with Down's syndrome, 18 with intracranial hemorrhage, 10 with cerebral infarction, and 10 elderly patients without any neurologic disorder). All cerebrovascular amyloid deposits in these 46 cases were consistently immunoreactive to anti-beta protein antibody. However, in nine cases some vascular walls with strong beta protein immunoreactivity also reacted less intensely with the anti-cystatin C antiserum. Of these nine cases, seven showed relatively heavy cerebrovascular amyloid deposition, and all seven had suffered a fatal subcortical hemorrhage presumably caused by cerebral amyloid angiopathy. Previous limited studies have suggested that the amyloid protein seen in elderly individuals with cerebral amyloid angiopathy is composed of beta protein. However, subcortical hemorrhage rarely occurs in such individuals. Our study shows that aged patients with different brain disorders commonly suffer from beta protein-type cerebral amyloid angiopathy, and we also suggest that the severity of beta protein-type cerebrovascular amyloid deposition is a fundamental factor in cerebral amyloid angiopathy-induced brain hemorrhage in the elderly. The nature of the cystatin C-immunoreactive substance in some of these vascular lesions is uncertain, but it might conceivably play an additional important role in the pathogenesis of brain hemorrhage in these cases.
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PMID:Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to beta protein and cystatin C. 221 20

Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.
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PMID:Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients. 257 69

Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral amyloid angiopathy. Of the autopsied cases 59 had senile plaques and cerebral amyloid angiopathy was also found in 36 of them. Both senile plaques and the blood vessel amyloid stained positively with beta-protein antibodies, and five of them also showed a positive reaction to cystatin C antibodies. These cystatin C positive cases were three males aged 76, 80 and 83, and one female 93 years old and the fifth case was a female aged 47 with Down's syndrome.
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PMID:Dementia with non-hereditary cystatin C angiopathy. 269 Jan 11

Cerebral amyloid angiopathy (CAA) refers to a group of hereditary (hereditary cerebral hemorrhage with amyloidosis, HCHWA and sporadic (SCAA) disorders characterized by amyloid fibril deposition restricted to the leptomeningeal and cortical vasculature leading to recurrent hemorrhagic and/or ischemic accidents. On clinical and biochemical grounds, two forms of HCHWA can be distinguished. The amyloid subunit of the HCHWA of Icelandic origin is related to Cystatin C, while amyloid from patients of Dutch origin (HCHWA-D) is related to the beta-protein (or A4), the main component of vascular and plaque core amyloid in Alzheimer's disease (AD) and Down's syndrome (DS) [corrected]. SCAA is an increasingly recognized cause of stroke in normotensive individual amounting to 5-10% of all cerebrovascular accidents. We now report the isolation and partial amino acid sequence of the amyloid subunit from a case of SCAA and a new case of HCHWA-D. The recognition that a heterogeneous group of diseases are linked by similar pathological and chemical features suggests that diversity of etiological factors may promote a common pathogenetic mechanism leading to amyloid-beta (A beta) deposition, and open new ways of research in AD and CAA as they are related to dementia and stroke.
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PMID:Beta-protein deposition: a pathogenetic link between Alzheimer's disease and cerebral amyloid angiopathies. 305 68

This article describes 136 patients with hereditary cerebral haemorrhages; all patients belonged to families (originally) resident in Katwijk (The Netherlands). Cases of hereditary cerebral haemorrhage have also been reported in NW-Iceland, and in the Dutch coastal village of Scheveningen. Katwijk is a Dutch fishing-village, located 20 miles north of Scheveningen. These 136 cases were encompassed in three large pedigrees, and the disorder followed an autosomal dominant mode of inheritance. No connection between the pedigrees from Iceland, Scheveningen and Katwijk has as yet been established. In our series, sclerosis with amyloid deposits could be observed in roughly a quarter of the small arteries and arterioles in the cerebral cortex and the covering arachnoid. The pathological vessels were irregularly distributed in areas and clusters, possibly leading to superficial cerebral infarcts and, secondarily, to haemorrhages. Our findings are identical with those described in patients from Scheveningen, but different from the Icelandic group. In addition to some differences in the age at onset and in the distribution of the angiopathy, it has recently been demonstrated that the amyloid in our patients is constituted by a microprotein which shows a homology to the beta-protein in Alzheimer's disease and Down's syndrome, while the amyloid in Icelandic cases is formed by an aggregation of cystatin C (gamma trace). An unexpected finding in most of our patients is the accumulation of senile plaque-like lesions in the cerebral cortex. We did not observe Alzheimer's fibrillary tangles in any of our cases.
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PMID:Hereditary cerebral haemorrhage caused by cortical amyloid angiopathy. 321 24

Amyloid deposition is a prominent feature of a number of brain disorders, in which amyloid fibrils are found within blood vessel walls, the neuropil (neuritic plaques), neurons (neurofibrillary tangles). These include Alzheimer's disease (AD), AD changes associated with Down's syndrome, neurologically asymptomatic amyloidosis, Parkinson dementia of Guam, hereditary cerebral hemorrhage with amyloidosis of Icelandic origin (HCHWA-I), hereditary cerebral hemorrhage with amyloidosis of Dutch origin (HCHWA-D), and sporadic cerebral amyloid angiopathy (SCAA). Recently it was shown that the amyloid deposits in AD, Parkinson dementia of Guam, and HCHWA-D are formed by a similar 4-kd polypeptide called beta-protein. Because the nature of the amyloid deposits in other types of cerebral amyloidosis is not known, we have conducted immunocytochemical studies on brains from autopsy cases of AD, HCHWA-D, SCAA and neurologically asymptomatic elderly individuals. Brains from two subjects without neurologic involvement were used as controls. Sections from these specimens were incubated with rabbit polyclonal antibodies against 1) a synthetic peptide of 28 residues (anti-SP28), homologous to the NH2-terminal sequence of the beta-protein, 2) the main amyloid component of the HCHWA-I, a variant of cystatin C, and 3) purified fraction of neurofibrillary tangles. In all cases, anti-SP28 antibody specifically stained amyloid deposits in leptomeningeal and cortical vessels and neuritic plaques. These findings demonstrate that the amyloid deposits of SCAA and aged brains are composed of a protein antigenically similar to AD, HCHWA-D, and Parkinson dementia of Guam beta-protein, suggesting that all of these clinically and etiologically different morbid conditions are pathogenetically related. On this basis, they can be tentatively grouped as beta-protein deposition diseases. In addition, we found that HCHWA-D and SCAA vessels were mainly affected, while in AD parenchymal involvement predominates. These differences in the localization and extent of beta-protein deposits may account from the predominance of vascular complications in HCHWA-D and SCAA and of dementia in AD.
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PMID:Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein. 332 21


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